The development of targeted particles for the treatment and detection of human diseases is expected to result in an explosion of the market for this class of biomaterials. In some cases, particles are functionalized with targeted molecules for the specific delivery of particles to a subset of cells, tissues, or organs. The delivery of particles is mediated by specific binding of targeting molecules with distinct chemical moieties that are present on the desired target. This approach has several limitations. First, it requires unique chemical moieties on the cells, tissue, or organ being targeted in order to achieve the desired specificity. And it requires the availability of high affinity targeting molecules that preferentially bind the unique chemical moiety on the cell, tissue, or organ. One problem with this approach is that there are a myriad of potentially useful targets and targeting molecules that have not yet been isolated and/or characterized.
In addition, other biophysiochemical characteristics of the targeted particles frequently need to be optimized in order to make them useful for in vitro or in vivo applications, for example, composition of the particle, surface characteristics, surface charge, and particle size. These many possibilities lead to a very large number of possible particle formulations. Individual evaluation of all these formulations or even a portion of them in vivo would require an equal or larger number of animals. Alternatively, particles could be initially screened using cell-based systems, following which promising formulations could be further evaluated in vivo. However, the results of in vitro evaluations are often not recapitulated by in vivo outcomes. For example, rapid clearance of particles by the liver, spleen, lung, lymphatic system, or bone marrow, the microenvironment of inflammation, or the unique features of tumor microenvironment, e.g., the tumor microvasculature, are not easily reproduced in in vitro models.
Therefore, given these significant drawbacks to current approaches for engineering particles, there remains a need for an efficient system that can be used to identify particles with particular characteristics, including targeting, cell uptake, pharmacokinetics, clinical efficacy, and so forth.